Current and Potential Developments of Cortisol Aptasensing towards Point-of-Care Diagnostics (POTC)
Anxiety is a psychological problem that often emerges during the normal course of human life. The detection of anxiety often involves a physical exam and a self-reporting questionnaire. However, these approaches have limitations, as the data might lack reliability and consistency upon application to the same population over time. Furthermore, there might be varying understanding and interpretations of the particular question by the participant, which necessitating the approach of using
... -based measurement for stress diagnosis. The most prominent biomarker related to stress, hormone cortisol, plays a key role in the fight-or-flight situation, alters the immune response, and suppresses the digestive and the reproductive systems. We have taken the endeavour to review the available aptamer-based biosensor (aptasensor) for cortisol detection. The potential point-of-care diagnostic strategies that could be harnessed for the aptasensing of cortisol were also envisaged. 2 of 13 increases heart rate and blood pressure, and represses growth, and digestive and reproductive activities. Cortisol is also involved in the maintenance of energetic balance  . It also has a function in the mediation of life history trade-offs  and allows for individuals to respond to disturbances in their environment  . The glucocorticoids, including cortisol, repress the production of CRH and ACTH, as a negative feedback response  . Since cortisol is the primary end product of the HPA axis, it can be employed as an amenable biomarker for the diagnosis of stress. A significant deviation in the cortisol level from the normal range in sweat, serum, and saliva is found to be associated with stress conditions     substantiating the use of cortisol as a suitable biomarker for stress. A potential biomarker of chronic disease defined by the recent use of hair cortisol measurements prove that it gives a retrospective index of incorporating cortisol secretion over a period of several months [12, 13] . Over the last 20 years, hair sample testing has increased in recognition and attention, especially for forensic purposes and the detection of illegal drugs. This is because hair can keep a relatively long-term record of retrospective levels of various biomarkers in the body  . High-performance liquid chromatography (HPLC) ion spray mass spectrometry has been developed for hair cortisol assay [15, 16] . Increased hair cortisol in rhesus macaques has been linked with a prolonged stressful experience. The immunoassay for testing hair cortisol has been developed by Davenport et al.  during the third trimester of pregnancy. Kirschbaum et al.  found that increased cortisol production has been systemically incorporated into growing hair by using the same method. It has been able to provide a retrospective long-term history of cortisol exposure for up to six months. A long-term follow-up study in the same individual can use these findings to indicate the use of hair for sample cortisol levels. It also has a potential for biomarker use in stress applications. Another famous cortisol sample type is by using blood or serum. Even though limited use in the clinical laboratory, serological methods are able to provide high sensitivity and specificity  . Dispersion to all water spaces of the body, such as saliva, serum, and urine, is the characteristic of cortisol secreted from adrenal glands. Urinary measures have the drawback of the inability to determine rapid changes in the cortisol level. In clinical and research settings, serum measures are often used but the stress from the venipuncture itself elevates the level of cortisol. Moreover, to perform daily serial blood collection is not practical. Contrarily, salivary cortisol samples benefit from easy collection. It is also present in the form of a bioactive fraction, but not in cortisol bound to cortisol-binding globulin (CBG) or other proteins  . Using anti-cortisol antibodies, many immune-sensing applications of cortisol have been developed for the diagnostic detection of stress, as summarized in Table 1 . The structure of cortisol is illustrated in Figure 1 .